# SMARCB1 regulated SWI/SNF complex function in Malignant Rhabdoid Tumors

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2022 · $375,150

## Abstract

PROJECT SUMMARY
A research program will be undertaken to study SMARCB1-regulated SWI/SNF complex function in malignant
rhabdoid tumors. Over the past few years, major cancer genome sequencing studies have identified frequent
inactivating mutations of mammalian SWI/SNF chromatin remodeling complex in over 25% of human cancers.
Despite the prevalence of SWI/SNF mutations, the contributions of these alterations to tumorigenesis remain
unclear. SMARCB1, a core subunit of the complex, was the first subunit linked to cancer when it was found to
be recurrently mutated in almost all cases of malignant rhabdoid tumors (RT). While studies using genetically
engineered mouse models have firmly established SMARCB1 as a tumor suppressor, the epigenetic mechanism
by which SMARCB1 mutation drives tumorigenesis remains elusive. The central hypothesis is that the
biochemical diversity of the SWI/SNF complex composition determines its function in proper chromatin targeting
to maintain discrete chromatin landscapes and transcriptional programs. Mutation of SMARCB1 leads to
aberrant intra- and inter-complex protein-protein interactions that influence chromatin targeting, which
consequently alters chromatin landscapes and higher-order structures, and promote an oncogenic epigenome
and transcriptome. The objective is to determine the role of SMARCB1 in SWI/SNF subcomplex formation and
the impact of these dynamics on chromatin targeting and higher-order chromatin structure. Our ultimate goal is
to determine the fundamental epigenetic mechanism(s) by which loss of this chromatin regulatory subunit drives
rhabdoid tumor development. To test this hypothesis, we will use a combination of cutting edge biochemical,
molecular, and high-throughput sequencing technologies to move forward the program through the following
specific aims: Aim 1, Determine SMARCB1 regulated SWI/SNF subcomplex assembly dynamics and identify
SWI/SNF interactome in rhabdoid tumors; Aim 2, Determine the chromatin targeting activities of SWI/SNF
subcomplexes and their relationship with other epigenetic regulators in rhabdoid tumors; Aim 3, Define higher-
order chromatin structures regulated by the SWI/SNF complex in rhabdoid tumors.

## Key facts

- **NIH application ID:** 10377519
- **Project number:** 5R01CA259850-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Xiaofeng Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,150
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377519

## Citation

> US National Institutes of Health, RePORTER application 10377519, SMARCB1 regulated SWI/SNF complex function in Malignant Rhabdoid Tumors (5R01CA259850-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10377519. Licensed CC0.

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